Dataset Information

Dose-response relationship between genetically proxied average blood glucose levels and incident coronary heart disease in individuals without diabetes mellitus.

ABSTRACT:

Aims/hypothesis

Our aim was to investigate the relationship between average blood glucose levels and incident CHD in individuals without diabetes mellitus.

Methods

To investigate average blood glucose levels, we studied HbA_1c as predicted by 40 variants previously shown to be associated with both type 2 diabetes and HbA_1c. Linear and non-linear Mendelian randomisation analyses were performed to investigate associations with incident CHD risk in 324,830 European ancestry individuals from the UK Biobank without diabetes mellitus.

Results

Every one mmol/mol increase in genetically proxied HbA_1c was associated with an 11% higher CHD risk (HR 1.11, 95% CI 1.05, 1.18). The dose-response curve increased at all levels of HbA_1c, and there was no evidence favouring a non-linear relationship over a linear one.

Conclusions/interpretations

In individuals without diabetes mellitus, lowering average blood glucose levels may reduce CHD risk in a dose-dependent way.

SUBMITTER: Burgess S

PROVIDER: S-EPMC7940279 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Dose-response relationship between genetically proxied average blood glucose levels and incident coronary heart disease in individuals without diabetes mellitus.

Burgess Stephen S Malik Rainer R Liu Bowen B Mason Amy M AM Georgakis Marios K MK Dichgans Martin M Gill Dipender D

Diabetologia 20210126 4

<h4>Aims/hypothesis</h4>Our aim was to investigate the relationship between average blood glucose levels and incident CHD in individuals without diabetes mellitus.<h4>Methods</h4>To investigate average blood glucose levels, we studied HbA<sub>1c</sub> as predicted by 40 variants previously shown to be associated with both type 2 diabetes and HbA<sub>1c</sub>. Linear and non-linear Mendelian randomisation analyses were performed to investigate associations with incident CHD risk in 324,830 Europe ...[more]

PMID: 33495845

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Project description:Rationale & objectiveBiomarkers of kidney disease progression have been identified in individuals with diabetes and underlying chronic kidney disease (CKD). Whether or not these markers are associated with the development of CKD in a general population without diabetes or CKD is not well established.Study designProspective observational cohort.Setting & participantsIn the Atherosclerosis Risk in Communities) study, 948 participants were studied.ExposuresThe baseline plasma biomarkers of kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), soluble urokinase plasminogen activator receptor (suPAR), tumor necrosis factor receptor 1 (TNFR-1), tumor necrosis factor receptor 2 (TNFR-2), and human cartilage glycoprotein-39 (YKL-40) measured in 1996-1998.OutcomeIncident CKD after 15 years of follow-up defined as ≥40% estimated glomerular filtration rate decline to <60 mL/min/1.73 m2 or dialysis dependence through United States Renal Data System linkage.Analytical approachLogistic regression and C statistics.ResultsThere were 523 cases of incident CKD. Compared with a random sample of 425 controls, there were greater odds of incident CKD per 2-fold higher concentration of KIM-1 (OR, 1.49; 95% CI, 1.25-1.78), suPAR (OR, 2.57; 95% CI, 1.74-3.84), TNFR-1 (OR, 2.20; 95% CI, 1.58-3.09), TNFR-2 (OR, 2.03; 95% CI, 1.37-3.04). After adjustment for all biomarkers, KIM-1 (OR, 1.42; 95% CI, 1.19-1.71), and suPAR (OR, 1.86; 95% CI, 1.18-2.92) remained associated with incident CKD. Compared with traditional risk factors, the addition of all 6 biomarkers improved the C statistic from 0.695-0.731 (P < 0.01) and using the observed risk of 12% for incident CKD, the predicted risk gradient changed from 5%-40% (for the 1st-5th quintile) to 4%-44%.LimitationsBiomarkers and creatinine were measured at one time point.ConclusionsHigher levels of KIM-1, suPAR, TNFR-1, and TNFR-2 were associated with higher odds of incident CKD among individuals without diabetes.Plain-language summaryFor people with diabetes or kidney disease, several biomarkers have been shown to be associated with worsening kidney disease. Whether these biomarkers have prognostic significance in people without diabetes or kidney disease is less studied. Using the Atherosclerosis Risk in Communities study, we followed individuals without diabetes or kidney disease for an average of 15 years after biomarker measurement to see if these biomarkers were associated with the development of kidney disease. We found that elevated levels of KIM-1, suPAR, TNFR-1, and TNFR-2 were associated with the development of kidney disease. These biomarkers may help identify individuals who would benefit from interventions to prevent the development of kidney disease.

Project description:Aims/hypothesisSleep duration is a risk factor for incident diabetes mellitus and CHD. The primary aim of the present study was to investigate, in sex-specific analyses, the role of incident diabetes as the possible biological mechanism for the reported association between short/long sleep duration and incident CHD. Considering that diabetes is a major risk factor for CHD, we hypothesised that any association with sleep duration would not hold for cases of incident CHD occurring before incident diabetes ('non-diabetes CHD') but would hold true for cases of incident CHD following incident diabetes ('diabetes-CHD').MethodsA total of 6966 men and 9378 women aged 45-73 years from the Malmö Diet Cancer Study, a population-based, prospective cohort, who had answered questions on habitual sleep duration and did not have a history of prevalent diabetes or CHD were included in the analyses. Incident cases of diabetes and CHD were identified using national registers. Sex-specific Cox proportional hazards regression models were stratified by BMI and adjusted for known covariates of diabetes and CHD.ResultsMean follow-up times for incident diabetes (n = 1137/1016 [men/women]), incident CHD (n = 1170/578), non-diabetes CHD (n = 1016/501) and diabetes-CHD (n = 154/77) were 14.2-15.2 years for men, and 15.8-16.5 years for women. In men, short sleep duration (< 6 h) was associated with incident diabetes (HR 1.35, 95% CI 1.01, 1.80), CHD (HR 1.41, 95% CI 1.06, 1.89) and diabetes-CHD (HR 2.34, 95% CI 1.20, 4.55). Short sleep duration was not associated with incident non-diabetes CHD (HR 1.35, 95% CI 0.98, 1.87). Long sleep duration (≥ 9 h) was associated with incident diabetes (HR 1.37, 95% CI 1.03, 1.83), CHD (HR 1.33, 95% CI 1.01, 1.75) and diabetes-CHD (HR 2.10, 95% CI 1.11, 4.00). Long sleep duration was not associated with incident non-diabetes CHD (HR 1.33, 95% CI 0.98, 1.80). In women, short sleep duration was associated with incident diabetes (HR 1.53, 95% CI 1.16, 2.01), CHD (HR 1.46, 95% CI 1.03, 2.07) and diabetes-CHD (HR 2.88, 95% CI 1.37, 6.08). Short sleep duration was not associated with incident non-diabetes CHD (HR 1.29, 95% CI 0.86, 1.93).Conclusions/interpretationThe associations between sleep duration and incident CHD directly reflect the associations between sleep duration and incident diabetes. Incident diabetes may thus be the explanatory mechanism for the association between short and long sleep duration and incident CHD.

Dataset Information

Dose-response relationship between genetically proxied average blood glucose levels and incident coronary heart disease in individuals without diabetes mellitus.

Aims/hypothesis

Methods

Results

Conclusions/interpretations

Publications

Dose-response relationship between genetically proxied average blood glucose levels and incident coronary heart disease in individuals without diabetes mellitus.

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